Our analysis of the mechanisms by which the cyclic AMP content of brain cells is regulated will be continued along three lines: 1. Studies utilizing slices of rat cerebral cortex will examine the effects of destruction of adrenergic nerve endings with 6-hydroxydopamine (6- OHDA) on the expression of catecholamine-stimulated adenylate cyclase activity. Specifically, the effect of 6-OHDA given to newborn rats will be examined in terms of its effect on the time course of ontogenetic development of the catecholamine-stimulated and the adenosine-stimulated adenylate cyclase. 2. Studies utilizing explant cultures of cerebral cortex from newborn rats will examine the time course of development of the agonist-sensitive adenylate cyclase activities and will attempt to characterize their pharmacological properties for comparison with agonist-sensitivity in slices of cerebral cortex. 3. Studies utilizing cultured human astrocytoma cells will attempt to characterize the effect of prostaglandins on adenylate cyclase activity. The analysis will involve the measurement of adenylate cyclase activity in cell homogenates and changes in cyclic AMP content in whole cells. An attempt will be made to correlate the effects of prostaglandins on adenylate cyclase activity and binding of H3-prostaglandin E1 to membrane fragements or whole cells.